Objective "Functional activity of proteins is tightly controlled via reversible post-translational modifications including phosphorylation, acetylation and ubiquitylation. These modifications enable the orchestration of cellular responses to a wide variety of stimuli. Due to these modifications, proteomes are overwhelmingly complex. Progress in the field has been greatly accelerated by the development of novel approaches to study these post-translational modifications at a proteome-wide scale using the sensitivity and robustness of mass spectrometry (MS). This has enabled the identification of thousands of dynamically regulated phosphorylation, acetylation and ubiquitylation sites by MS. The functional significance of these modifications is now being addressed worldwide at an unprecedented scale. In contrast, global understanding of ubiquitin-like signalling networks in a site-specific manner is very challenging.Over the last few years, my lab has established novel methodology for the purification and identification of endogenous SUMO target proteins and SUMOylation sites of endogenous targets. The first aim of this project is to uncover small ubiquitin-like modifier (SUMO) signalling pathways in a site-specific manner at a proteome-wide level.The second aim of this project is to reveal how SUMOylation cooperates with ubiquitylation to maintain genome integrity. SUMOylation plays a critical role during the DNA damage response, an important barrier against genome instability linked diseases including cancer and neurodegeneration. Selected target proteins will be studied at the functional and mechanistic level to obtain novel insight in cellular processes that protect against genome instability.The developed methodology is generic and can be applied to study all ubiquitin-like proteins at a proteome-wide level in a site-specific manner, enabling global understanding of ubiquitin-like signalling networks in health and disease." Fields of science natural sciencesbiological sciencesneurobiologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomicsmedical and health sciencesclinical medicineoncologynatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesgeneticsgenomes Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Call for proposal ERC-2012-StG_20111109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution ACADEMISCH ZIEKENHUIS LEIDEN EU contribution € 1 517 698,80 Address ALBINUSDREEF 2 2333 ZA Leiden Netherlands See on map Region West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Activity type Higher or Secondary Education Establishments Administrative Contact Karin Wibier (Ms.) Principal investigator Alfredus Cornelis Otto Vertegaal (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all ACADEMISCH ZIEKENHUIS LEIDEN Netherlands EU contribution € 1 517 698,80 Address ALBINUSDREEF 2 2333 ZA Leiden See on map Region West-Nederland Zuid-Holland Agglomeratie Leiden en Bollenstreek Activity type Higher or Secondary Education Establishments Administrative Contact Karin Wibier (Ms.) Principal investigator Alfredus Cornelis Otto Vertegaal (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
